@article { ISI:000280605900013,
	title = {Coupling growth-factor engineering with nanotechnology for therapeutic angiogenesis},
	journal = {Proceedings of the National Academy of Sciences of the United States of America},
	volume = {107},
	number = {31},
	year = {2010},
	month = {AUG},
	pages = {13608-13613},
	publisher = {NATL ACAD SCIENCES},
	address = {2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA},
	abstract = {<p>Therapeutic angiogenesis is an emerging paradigm for the management of ischemic pathologies. Proangiogenic Therapy is limited, however, by the current inability to deliver angiogenic factors in a sustained manner at the site of pathology. In this study, we investigated a unique nonglycosylated active fragment of hepatocyte growth factor/scatter factor, 1K1, which acts as a potent angiogenic agent in vitro and in a zebrafish embryo and a murine matrigel implant model. Furthermore, we demonstrate that nanoformulating 1K1 for sustained release temporally alters downstream signaling through the mitogen activated protein kinase pathway, and amplifies the angiogenic outcome. Merging protein engineering and nanotechnology offers exciting possibilities for the treatment of ischemic disease, and furthermore allows the selective targeting of downstream signaling pathways, which translates into discrete phenotypes.</p>},
	keywords = {cardiovascular disease, HGF/SF, ischemic disease, nanoparticle, protein engineering},
	issn = {0027-8424},
	doi = {10.1073/pnas.1006007107},
	author = {Roy, Rituparna Sinha and Soni, Shivani and Harfouche, Rania and Vasudevan, Pooja R. and Holmes, Oliver and de Jonge, Hugo and Rowe, Arthur and Paraskar, Abhimanyu and Hentschel, Dirk M. and Chirgadze, Dimitri and Blundell, Tom L. and Gherardi, Ermanno and Mashelkar, Raghunath Anant and Sengupta, Shiladitya}
}
@article {47126,
	title = {Repurposing the McoTI-II rigid molecular scaffold in to inhibitor of {\textquoteleft}papain superfamily{\textquoteright} cysteine proteases},
	journal = {Pharmaceuticals},
	volume = {14},
	year = {2021},
	month = {JAN},
	pages = {7},
	type = {Article},
	abstract = {<p>Clan C1A or {\textquoteleft}papain superfamily{\textquoteright} cysteine proteases are key players in many important physiological processes and diseases in most living systems. Novel approaches towards the development of their inhibitors can open new avenues in translational medicine. Here, we report a novel design of a re-engineered chimera inhibitor Mco-cysteine protease inhibitor (CPI) to inhibit the activity of C1A cysteine proteases. This was accomplished by grafting the cystatin first hairpin loop conserved motif (QVVAG) onto loop 1 of the ultrastable cyclic peptide scaffold McoTI-II. The recombinantly expressed Mco-CPI protein was able to bind with micromolar affinity to papain and showed remarkable thermostability owing to the formation of multi-disulphide bonds. Using an in silico approach based on homology modelling, protein-protein docking, the calculation of the free-energy of binding, the mechanism of inhibition of Mco-CPI against representative C1A cysteine proteases (papain and cathepsin L) was validated. Furthermore, molecular dynamics simulation of the Mco-CPI-papain complex validated the interaction as stable. To conclude, in this McoTI-II analogue, the specificity had been successfully redirected towards C1A cysteine proteases while retaining the moderate affinity. The outcomes of this study pave the way for further modifications of the Mco-CPI design for realizing its full potential in therapeutics. This study also demonstrates the relevance of ultrastable peptide-based scaffolds for the development of novel inhibitors via grafting.</p>
},
	keywords = {Cathepsin, Clan CA cysteine proteases, cyclotide, cystatin, McoTI-II, papain, protein engineering},
	doi = {10.3390/ph14010007},
	author = {Mishra, Manasi and Singh, Vigyasa and Tellis, Meenakshi B. and Joshi, Rakesh S. and Singh, Shailja}
}
